Boron trifluoride → (2-Fluoro-5-methoxy-4-nitrophenyl)methanol
Reaction equation
[F:1][C:2]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[C:8]([O:14][CH3:15])=[CH:7][C:3]=1[C:4](O)=[O:5].[BH4-].[Na+].B(F)(F)F>C1COCC1>[F:1][C:2]1[CH:10]=[C:9]([N+:11]([O-:13])=[O:12])[C:8]([O:14][CH3:15])=[CH:7][C:3]=1[CH2:4][OH:5]Participants
Conditions
- Temperature
- 0 °C
Procedure
A solution of 2-fluoro-5-methoxy-4-nitrobenzoic acid (Compound 130E, 1.60 g, 7.44 mmol) in THF (23.6 mL) is slowly charged with sodium borohydride (0.633 g, 16.8 mmol) and stirred for 5 minutes. A solution of boron trifluoride, ethyl ether complex (0.895 mL, 7.26 mmol) in THF (7.85 mL) is added to the reaction mixture. The resulting solution is heated at reflux for 4 h. The reaction mixture was cooled to 0° C., then quenched with ice (15 mL) and diluted with ether (25 mL) and 2 N NaOH (10 mL). The ether layer was washed with brine (15 mL), dried over Na2SO4, filtered and concentrated under reduced pressure to yield an off-white solid, 1.45 g (97% yield). This material was used without any further purification. 1H NMR (CDCl3, 400 MHz): δ=3.99 (s, 3 H), 4.86 (s, 2 H), 7.29 (d, J=5.81 Hz, 1 H), 7.64 (d, J=9.09 Hz, 1 H). MS (ES+): m/z 202.05 [MH+] (TOF, polar).
Workup
- temperatureThe resulting solution is heated
- temperatureat reflux for 4 h
- customquenched with ice (15 mL)
- additiondiluted with ether (25 mL) and 2 N NaOH (10 mL)
- washThe ether layer was washed with brine (15 mL)
- dry with materialdried over Na2SO4
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customto yield an off-white solid, 1.45 g (97% yield)
- customThis material was used without any further purification
Sources & evidence
- ORD record
- ord-2db6025051c04839ba3badf213791b10
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09096624B2
Reaction notes
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